Supporting Statement A
Stem Cell Therapeutic Outcomes Database
OMB Control No. 0915-0310
Revision Request
The Health Resources and Services Administration (HRSA) is requesting that the Office of Management and Budget continue approval of the data collection instruments for the Stem Cell Therapeutic Outcomes Database (SCTOD), a component of the C.W. Bill Young Cell Transplantation Program (the Program). These instruments provide the data elements required to fulfill the contractual requirements of the SCTOD, as outlined below. They were developed by the Center for International Blood and Marrow Transplant Research at the Medical College of Wisconsin, in collaboration with hematopoietic cell transplantation experts in the United States and the international arena.
The Stem Cell Therapeutic and Research Act of 2005, Public Law (Pub. L.) 109–129, as amended by the Stem Cell Therapeutic and Research Reauthorization Act of 2015, Public Law 114-104.
The information collection activities described in this submission are reauthorized by the
Stem Cell Therapeutic and Research Reauthorization Act of 2015, Public Law 114–104, which was signed into law on December 18, 2015. Section 379A of the Public Health Service (PHS) Act (42 U.S.C. 274l) is amended to require the Secretary, acting through the Administrator of HRSA, to establish and maintain the C.W. Bill Young Cell Transplantation Program.
The Stem Cell Therapeutic Outcomes Database
Congress has legislated that outcomes data must be collected on all patients “who have been recipients of a stem cell therapeutics product (including bone marrow, cord blood, or other such product) from a donor.” This includes allogeneic transplants, both related and unrelated, where either the donor or the recipient resides in the U.S. The Center for International Blood and Marrow Transplant Research (CIBMTR) at the Medical College of Wisconsin was awarded the contract for the outcomes database in September 2006 and September 2012. As the recipient of this contract, the CIBMTR is responsible, with HRSA oversight, for the administration of this activity and the collection and analysis of the data.
The CIBMTR® (Center for International Blood and Marrow Transplant Research®) is a research collaboration between the National Marrow Donor Program® (NMDP)/Be The Match® and Medical College of Wisconsin. Transplant centers have long collaborated with the CIBMTR and the NMDP and have substantial experience with providing data in voluntary partnerships and networks. The Act establishes federal oversight of a standardized electronic system, and the CIBMTR uses their substantial experience and proven methods to collect the transplant data.
The CIBMTR is a voluntary organization involving approximately 400 transplant centers in 42 countries that have collaborated to share patient data and conduct scientific studies since 1972. This organization has collected outcomes data provided voluntarily (without HRSA oversight) by transplant centers worldwide on both allogeneic and autologous (patient’s own cells) hematopoietic cell transplants (HCTs), including data beyond the requirements of the contract for research. Hematopoietic stem cells are the cells responsible for continual regeneration of circulating blood cells throughout life; they are not embryonic stem cells. The CIBMTR has made these data available to investigators and physicians worldwide, providing physicians, scientists, policy makers and patients with the information they need to make the best possible clinical decisions and to advance the field.
The NMDP is the global leader in providing a cure to patients with life-threatening blood and marrow cancers like leukemia and lymphoma, as well as other diseases. The nonprofit organization manages the world’s largest registry of potential marrow donors and cord blood units, connects patients to their donor match for a life-saving marrow or umbilical cord blood transplant, and educates health care professionals and patients. The CIBMTR is subcontracting with the NMDP to help fulfill the contract requirements. The scope of data collection under this contract includes:
allogeneic1 transplantation for hematopoietic reconstitution using cells from donors not related to the patient;
allogeneic transplantation for hematopoietic reconstitution using cells from donors who are related to the patient; and
emerging clinical applications of cells derived from bone marrow, peripheral blood, and umbilical cord blood. (Defined as therapeutic applications of cells derived from the bone marrow, peripheral blood, or umbilical cord blood for purposes other than hematopoietic reconstitution.)
HRSA is responsible for establishing and maintaining a standardized database of allogeneic (related and unrelated donor) marrow and cord blood transplants performed in the United States. The Act requires that transplant centers performing these transplants provide patient outcomes data to this national system. Data collection on patient outcomes is required in order to be in compliance with the requirements of the Act and is critical to the successful implementation of the Program. Collected data are used to understand transplant activity, including trends in numbers of transplantations and emerging uses of cells, report outcomes, and for research use as outline in the Stem Cell Act as described below.
The data collection instruments included in this package are the Pre-TED (Transplant Essential Data), Post-TED (100-day, 6 month, 1 year, and annual) and the Product Form. The Product Form consists of the Infusion Insert, Infectious Disease Marker Insert and the Human Leukocyte Antigen or HLA Typing Insert. These instruments contain the data elements necessary to fulfill the broad requirements of the SCTOD as established in the authorizing legislation for all allogeneic transplants occurring in the United States or using a donor from the United States.
The requirements for data submission using the Pre-TED and the Post-TED are familiar to transplant centers. The CIBMTR has a long history of collecting similar data from transplant centers, and engages the scientific community in its efforts to maintain up-to-date data collection systems. The balance between collecting sufficient data to analyze patient outcomes versus minimizing the reporting burden on transplant centers to collect and submit such data has been carefully considered.
Graft characteristic data for cord blood units and unrelated donor grafts facilitated by the Program are collected within fourteen days of HCT on the Product Form. This form includes critical details of: procedures to facilitate stem cell collection; product collection, handling, transport, manipulation and storage; graft content including essential cell counts for engraftment; infectious contamination of cellular products; infusion timing and adverse events; and demographic information about the donor (includes the donor mother’s information for cord blood units). The HLA or tissue type and infectious disease marker sections of the Product Form collect information regarding degree and resolution of HLA-matching between donor and recipient, as well as the relevant infectious disease testing of the donor. These graft data, along with the outcomes data collected on the Pre-TED and Post-TED are essential data elements for the Program.
The data collected using these instruments meets the requirements of the Act in establishing a scientific database, providing data to Program components, and providing information for the required annual report on blood stem cell transplantation to the Secretary.
No new forms are being added. Existing instruments have been revised to reflect changes in transplant practice over time, and the need to accommodate these changes in reports and analyses of the data. The Post-TED form (used at 100-day, 6 month, 1 year, and annual) is being revised in this submission. The portion of the Product Form related to confirmation of HLA typing has minor changes to the identification and date fields to allow this form to more flexibly capture HLA typing data. The amount of time required to complete this form is unchanged. The Pre-TED form remains unchanged from the previously approved OMB submission. The CIBMTR will include the OMB number and expiration date in the upper right corner of each page of the approved instruments prior to using them.
The system for the outcomes database is electronic. Implementation of the data collection instruments includes reporting forms that can be downloaded or can be submitted electronically using the Web-based interface, called FormsNet 3.0. Virtually all U.S. HCT centers provide their data through the electronic system. Data collection instruments are accompanied by an instructions manual. The CIBMTR is acutely aware of the need to minimize the burden of data collection for transplant centers, and the electronic system is designed to streamline data submission wherever possible through smart navigation tools, electronic validation and auto-population of previously submitted fields. Transplant centers collect, store and report information using a variety of mechanisms ranging from paper forms and electronic software packages to Web interfaces.
FormsNet 3.0 allows for remote data entry of all transplant baseline and follow-up data by the transplant centers. This system is a single Web-based application for data entry, viewing, and auditing of recipient forms. Important features included in the system are:
24/7 accessibility;
create/edit forms and inserts;
create/edit all CIBMTR specific inserts;
create/edit confirmation of HLA typing and product forms;
audit trail and user interface;
data entry and form reconciliation; and
tools for monitoring accuracy and processes.
The system includes automated validation checks within and between forms; automatically generated error reports; field-level saving and field-level audit trails; review functions for center supervisors; forms due reporting; and the flexibility to add additional features. FormsNet 3.0 is fully compliant with Federal database security requirements as established by HRSA’s Office of Information Technology (OIT) and the Food and Drug Administration (FDA) 21 CFR Part 11; Electronic Records; Electronic Signatures Maintenance of Electronic Records and Computerized Systems Used in Clinical Trials.
The updated forms included with this application will be available in FormsNet 3.0 for data entry following approval from the U.S. Office of Management and Budget (OMB).
The CIBMTR has established a system for data collection within the United States for HCT that is not duplicated, to any significant degree, by any other U.S. entity. The CIBMTR and the NMDP have worked together to develop the systems that will capture the required outcomes reporting. For purposes of this database, all data collection for the HCT outcomes is collected using a single set of instruments that encompasses all allogeneic transplants performed in the United States, including umbilical cord blood transplantation. No other organization in the United States currently collects these data in a systematic way that would represent a duplication of effort.
This information collection does not impact small businesses or other small entities.
The information collection activity outlined in this request is required under the Stem Cell Therapeutic and Research Act of 2005, as amended by the Stem Cell Therapeutic and Research
Reauthorization Act of 2015, Public Law 114–104 (the Act). The Act mandates the collection of data for the outcomes database. The data that are to be collected have been carefully considered by the broad transplant community. These data, and the time points for data collection, represent a parsimonious solution to the trade-offs of data collection and reporting burden to those providing data and the need to have comprehensive data to fulfill the requirements of the SCTOD. The data reporting schedule and the proposed instruments represent the consensus of the transplant community regarding data that would be essential to understand the broad requirements of the Program. These requirements include numbers of transplants facilitated by the Program, numbers of transplants performed annually in the United States, outcomes of those transplant procedures, long-term outcomes of blood stem cell transplantation, effective use of cord blood units for transplantation, and alternative uses of cells derived from bone marrow and cord blood. Additionally, these requirements include annual transplant center specific survival reports to be made available to patients, physicians, and the general public. A representative forum of U.S. HCT centers, scientists, patients, and payers participates in discussion and revision of data elements needed to support the center specific analysis every other year.
CIBMTR will continue to collect data from HCT centers on the following schedule: baseline, 100 days after HCT, 6 months after HCT, 1 year after HCT, annually for 6 years after HCT and biennially thereafter, and, if the patient dies, cause of death data. Baseline data are collected within 30 days of the HCT and includes patient demographics, disease characteristics and status, co-morbidities, HCT procedure characteristics including preparative regimen and GVHD prophylaxis, graft source, donor type and degree of HLA matching and graft manipulation. Graft characteristic data for cord blood units, including infused cell dose are collected within 60 days of HCT. These data are collected on the Pre-TED forms.
Data collected at 100 days and beyond includes hematopoietic recovery and engraftment1, serious complications including GVHD and second cancers, disease status, survival status, and cause of death. Subsequent procedures, including additional transplants or cellular therapy, are also collected. These data are due within 60 days of achieving the milestone date. These data are collected on the Post-TED form (the Post-TED form will be completed for all time points at or beyond 100-days after transplantation).
These requirements are well-established in U.S. transplant centers and represent a balance between collecting sufficient data to analyze HCT outcomes and minimizing the data submission burden.
Collecting less information than that proposed in the submitted data collection instruments threatens the ability to understand the type of transplant, the comorbid conditions of the patients who undergo transplantation, and the short-term and long-term results of the transplant procedures. Much of the data collected is essential to understanding and reporting differences in transplant outcomes across U.S. transplant centers in an equitable fashion, using data already proven, or commonly believed to affect outcomes by transplant experts and accrediting organizations. Collecting data at the proposed time points is not only essential to understand outcomes at various time points in the transplant process, but represent standard time points of assessment for allogeneic transplant recipients. These time points are also meant to reinforce the importance of follow-up assessments by transplant centers to avoid losing contact with transplant recipients in a system where recipients gradually become more remote from the tertiary care centers where allogeneic transplantation is performed.
If the information required in Section 379A(c) is not collected, HRSA will not be in compliance with the authorizing legislation. This information is required by the Secretary to report the following:
whether program funds for the SCTOD are fulfilling the mission of the C.W. Bill Young Cell Transplantation Program;
what types of transplants are being performed in the United States and for what clinical indications, and the outcomes of those transplants; and
outcomes of blood stem cell transplantation across transplant centers.
The data are collected in a manner fully consistent with the guidelines in 5 CFR 1320.5.
The 60-day notice required in 5 CFR 1320.8(d) was published in the Federal Register on May 18, 2016 (Volume 81, Number 96, Pages 31244- 31245. No comments were received.
In December 2007, CIBMTR implemented a standard dataset developed in collaboration with national and international partners. CIBMTR subsequently worked with the American Society for Blood and Marrow Transplantation (ASBMT) Quality Outcomes Committee to refine this dataset to better allow assessment of HCT outcomes across transplant centers (center-specific outcomes), such as including data on pre-HCT co-morbidities. This standard data set comprises the current OMB-approved TED forms and is collected on all patients. Collection of data captured on TED forms is a requirement for HCT center accreditation by the Foundation for the Accreditation of Cellular Therapy (FACT) and its European counterpart, the Joint Accreditation Committee of the International Society for Cellular Therapy and the EBMT (JACIE). Through its collaborations with Eurocord, the New York Blood Center and cord blood banks, CIBMTR has extensive expertise refining and validating data elements relevant to analyzing cord blood transplant outcomes and has worked with cord blood banks to ensure that collected common data elements include data necessary to address FDA reporting requirements.
These extensive discussions have led to international consensus on a set of common data elements that should be collected to understand outcomes of transplantation in general, and to meet the requirements of the Program. Since initially arriving at the standard dataset described above, the CIBMTR has continued to work with the national and international community to maintain those standards. These data elements are represented on the Pre-TED (baseline data), Post-TED (outcomes data) and Product Forms that are being submitted for OMB approval.
CIBMTR continues to promote international harmonization of HCT data standards and participates in the annual data standards review of the European Group for Blood and Marrow Transplantation (EBMT) and the Worldwide Network for Blood and Marrow Transplantation (WBMT) Transplant Center Committee. Broad acceptance of standards facilitates acquisition of data regarding HCTs done outside the U.S. with U.S. products. CIBMTR will continue to work with ASBMT, EBMT, WBMT, the Clinical Working Group of the World Marrow Donor Association (WMDA), cord blood banks (using the Cord Blood Data Working Group), and other Program members to achieve consensus on any revisions to the standard dataset and to ensure that it meets the needs of the Program to fulfill its contractual requirements to disseminate data, to perform center-specific analyses, to create cord blood inventory and adult donor registry models, and to capture data elements critical for understanding HCT outcomes while minimizing the data submission burden for HCT centers. It will continue to work with the Bone Marrow Coordinating Center, Cord Blood Coordinating Center and NMDP Histocompatibility Advisory Group to ensure that HLA data reflect current HLA matching algorithms.
Through the FormsNet electronic data capture system the CIBMTR collects data on patient demographics, pre-transplant disease characteristics and status, transplant procedures, including pre-transplant conditioning regimen and GVHD prophylaxis, graft source, donor type and degree of HLA matching, and graft manipulation, early and long-term outcomes including hematopoietic recovery, GVHD, disease relapse, survival, second cancers, and other complications. These data permit analysis of outcomes aggregated by disease, transplant modality, or transplant center. Currently, approximately 400 centers (including all U.S. centers performing allogeneic HCT) submit data to CIBMTR. FormsNet also collects information from donor/collection centers that allow characterization of the donor and cellular product, including cell counts and infectious disease testing. Data collection instruments accommodate sequential infusions and multiple graft sources.
Data collection instruments are reviewed on an established timeline to ensure that the most relevant data are being collected. Broad stakeholder participation in this process is accomplished through the 15 Working Committees, cord blood banks, the coordinating centers, and collaborative relationships with Eurocord, EBMT, WBMT, ASBMT and FACT. Similarly, transplant centers are represented in the form revision process, especially to meet the needs of the transplant center-specific survival analysis performed by the CIBMTR. Data collection instruments are accompanied by a detailed data dictionary that is updated regularly.
Respondents are not paid or rewarded.
The data collection instruments used for the SCTOD do not require information that could be used to directly identify transplant recipients. The CIBMTR’s subcontractor, the NMDP, utilizes a unique identification (ID) registration system for transplant recipients to avoid redundant reporting of transplant recipients across transplant centers and across time. This unique ID registration system exists within an isolated server and uses identifying information about transplant recipients provided by the transplant center to assign a unique ID number that does not contain personal identifiers. Subsequently, this unique number is used by the transplant center and other Program components to exchange data regarding transplant recipients for purposes of reporting outcomes to the Government.
The ID registration system and the exchange of data between entities exists within the context of the designation of the CIBMTR as a public health authority for purposes of the Health Insurance Portability and Accountability Act (HIPAA) as determined by the HHS Office of General Counsel and Office of Civil Rights (OCR) in fulfillment of the contract requirements (PHA letter attached). The Office of the General Counsel has determined, and OCR concurs, that the CIBMTR meets the Privacy Rule’s definition of a public health authority and is authorized by law to collect the information necessary for the SCTOD to fulfill its statutory purpose and functions. Under this analysis, transplant centers that are covered entities may disclose to the CIBMTR the individually identifiable health information collected by the SCTOD in order for the Database to comply with its statutory purposes. Additionally, the electronic systems used to create and maintain the unique ID system exist under the auspices of HRSA’s Office of Information Technology (OIT) Certification and Accreditation system.
Although the data collection instruments do not request direct identifiers, by virtue of the nature of reporting transplant outcomes required for the SCTOD contract, they request birth dates, procedure dates, complication and event dates, and death dates. These data are housed in secure electronic data systems which exist with certification and accreditation from HRSA OIT.
All reports and tabulated data released to the general public are in the form of aggregate summaries of information across patients and transplant centers.
There are no questions of a sensitive nature collected on the TED and Product Forms. The only patient-level identifying information is birth date, procedure and complication dates, and death dates. These are required for outcomes reporting for the SCTOD for HRSA. However, as detailed above, these data are maintained in secure and protected systems. Only aggregate data summarizing transplant activity and outcomes are included in reports published by the SCTOD on behalf of HRSA.
The estimate of average hour burden to complete data collection instruments is shown in Table 1. As Table 1 shows, an estimated 200 respondent U.S. transplant centers report transplant data to the CIBMTR using these reporting instruments. Reporting of transplant outcomes is required with greater frequency during the first year post-transplant. Subsequent transplant follow-up reporting is conducted annually. The cumulative number of annual Post-TED forms submitted by any given transplant center will increase in subsequent years. The increase in burden is due to an increase in the annual number of transplants being performed and the increasing survivorship after transplantation. Burden of data collection and reporting will vary by transplant center, as there is a large variation in the number of allogeneic transplants performed at transplant centers across the United States.
Table 1. Estimates of Average Annualized Hour Burden
|
Number of Respondents |
Responses per Respondent |
Total Responses |
Hours per Response |
Total Burden Hours |
Baseline Pre-TED (Transplant Essential Data) |
200 |
44 |
8,800 |
1.15 |
10,120 |
Product Form (includes Infusion, HLA, and Infectious Disease Marker inserts) |
200 |
33 |
6,600 |
1 |
6,600 |
100-Day Post-TED |
200 |
44 |
8,800 |
1.25 |
11,000 |
6-Month Post-TED |
200 |
36 |
7,200 |
1.15 |
8,280 |
12-Month Post-TED |
200 |
32 |
6,400 |
1.15 |
7,360 |
Annual Post-TED |
200 |
110 |
22,000 |
1.15 |
25,300 |
Total* |
200 |
|
59,800 |
|
68,660 |
*The total of 200 is the number of centers completing the form. The same group of 200 centers completes each of the forms.
The Pre-TED, Product Form, 100-Day Post-TED, 6-Month Post-TED, and 12-Month Post-TED will be collected on all patients during their first year of transplant. In subsequent years, patient outcomes will be reported on the Annual Post-TED form. There will be a gradual increase in the cumulative reporting burden over time commensurate with the number of survivors for which transplant centers must submit an Annual Post-TED.
There are no direct costs to respondent transplant centers other than their time spent completing the data collection instruments. There are no capital or start-up costs for respondents related to this effort. Web-based electronic data entry mechanisms and instructions on use of the applications will be available free of charge to transplant centers by the CIBMTR.
HRSA has planned and allocated resources for the efficient and effective management and use of the information to be collected, including the processing of the information in a manner that shall enhance the utility of information to agencies and the public. HRSA estimates an annual investment of approximately $4 million to be spent on all aspects of the contract for the operation of the Stem Cell Therapeutic Outcomes Database.
This is a revised collection of information with 52,260 being the existing hour burden inventory. This revision is requesting an estimated hour burden of 68,660 mainly due to the increased anticipated number of responses.
The data collected using the instruments outlined above populate a database for the SCTOD and are used for numerous analyses, reports, and publications.
Data collected for the SCTOD are shared with other components of the C.W. Bill Young Cell Transplantation Program in fulfillment of the goals and statutory charge of the Program. The electronic systems used by the CIBMTR provide outcomes data to HRSA, the umbilical cord blood banks, and the transplant programs themselves. The system accommodates pre-programmed queries for outcomes reporting and allows transplant centers and other appropriate entities to generate customized reports. Applications are being built to disseminate data regarding the quality characteristics of transplanted stem cell products to and from transplant centers, collection facilities, and cord blood banks.
The outcomes database is also used to prepare reports about the C.W. Bill Young Cell Transplantation Program for the Secretary, the Advisory Council on Blood Stem Cell Transplantation, HRSA, and the public.
The CIBMTR prepares an annual Transplant Center-Specific Survival Report for the Program outlining the specific survival rates for all transplant centers in the U.S. This is an extremely important report for patients and physicians, both for improving quality of care at transplant centers and for helping patients and their physicians make well informed choices about which transplant centers are most appropriate for each patient.
In addition, as required in section 379A(d) of the Act, the outcomes database makes relevant scientific information that does not contain individually identifiable information available to the public. This information is provided by CIBMTR in the form of summaries and data sets to encourage medical research and to provide information to transplant programs, physicians, patients, and cord blood banks.
This does not apply as the expiration date will be displayed.
This information collection fully complies with 5 CFR 1329.9. The certifications are included with the package. There are no exceptions to the certification.
List of Acronyms
ASBMT American Society for Blood and Marrow Transplantation
CIBMTR Center for International Blood and Marrow Transplant Research
EBMT European Group for Blood and Marrow Transplantation
FACT Foundation for the Accreditation of Cellular Therapy
FDA U.S. Food and Drug Administration
HCT Hematopoietic cell transplantation (i.e., bone marrow or cord blood transplantation or blood stem cell transplantation)
HHS U.S. Department of Health and Human Services
HIPAA Health Insurance Portability and Accountability Act
HLA Human Leukocyte Antigen
HRSA U.S. Health Resources and Services Administration
JACIE Joint Accreditation Committee of the International Society for Cellular Therapy
NMDP National Marrow Donor Program
OCR Office of Civil Rights
OIT HRSA’s Office of Information and Technology
OMB U.S. Office of Management and Budget
Program C.W. Bill Young Cell Transplantation Program
SCTOD Stem Cell Therapeutic Outcomes Database
TED Transplant Essential Data
WBMT Worldwide Network for Blood and Marrow Transplantation
WMDA World Marrow Donor Association
1 In an allogeneic transplant, a patient receives blood stem cells collected from a sibling or other related donor, or from an unrelated donor.
1 The process in which transplanted hematopoietic cells begin to grow in the bone marrow of the host and to produce new white blood cells, red blood cells and platelets.
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| File Title | TITLE (ALT T) |
| Author | Ruth Steenburg |
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| File Created | 2021-01-23 |